A Study to Assess Objective Endpoint Measurements of Response in Bacterial Skin Infections

September 25, 2019 updated by: Melinta Therapeutics, Inc.

A Phase 2 Exploratory Study of Objective Endpoints in Subjects With Acute Bacterial Skin and Skin Structure Infections Treated With Delafloxacin, Vancomycin, or Linezolid

The purpose of this study is to compare clinical response to the measurement techniques of several objective measures of clinical efficacy for use in future ABSSSI (Acute Bacterial Skin and Skin Structure Infection) clinical trials

Study Overview

Study Type

Interventional

Enrollment (Actual)

256

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Mobile, Alabama, United States, 36617
        • University of South Alabama Medical Center
      • Montgomery, Alabama, United States, 36106
        • Drug Research and Analysis Corp
    • California
      • Buena Park, California, United States, 90620
        • Southbay Pharma Research
      • Chula Vista, California, United States, 91911
        • eStudySite
      • La Mesa, California, United States, 91942
        • eStudySite
      • Los Angeles, California, United States, 90015
        • HealthCare Partners Medical Group
      • Oceanside, California, United States, 92056
        • eStudySite
      • Pasadena, California, United States, 91105
        • HealthCare Partners Medical Group
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Care Health Services
    • Florida
      • Edgewater, Florida, United States, 32132
        • Riverside Clinical Research
      • Jacksonville, Florida, United States, 32207
        • River City Clinical Research
      • Kissimmee, Florida, United States, 34741
        • Central Florida Internists
      • Orlando, Florida, United States, 32811
        • Central Florida Internists Medical
      • Saint Cloud, Florida, United States, 34769
        • Central Florida Internists
      • Temple Terrace, Florida, United States, 33617
        • Ronald Barbour, MD
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Southeast Regional Research Group
      • Decatur, Georgia, United States, 30030
        • Atlanta Institute For Medical Research, Inc
      • Savannah, Georgia, United States, 31406
        • Southeast Regional Research Group
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Paducah, Kentucky, United States, 42003
        • Four Rivers Clinical Research, Inc
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70810
        • Medical Development Centers, LLC
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri Health Care
    • Montana
      • Butte, Montana, United States, 59701
        • Mercury Street Medical Group, PLLC
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • eStudySite
    • New Jersey
      • Somers Point, New Jersey, United States, 08244
        • South Jersey Infectious Disease
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43215
        • Remington-Davis, Inc.
      • Lima, Ohio, United States, 45801
        • Ravi Kamepalli, MD
    • South Dakota
      • Rapid City, South Dakota, United States, 57702
        • Health Concepts
    • Texas
      • Houston, Texas, United States, 77002
        • Jennifer Johnson-Caldwell, MD
      • Houston, Texas, United States, 77005
        • Alan Nolasco, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult (≥ 18 years of age) men or women
  • Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception as determined by the investigator during participation in the study and for 30 days after the final dose of study drug
  • Female partners of male subjects should also use an additional reliable method of contraception during study and for 30 days after the final dose of study drug
  • Subjects must have a diagnosis of ABSSSI - one or more of the following 4 infection types: cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection
  • Subjects must have lymph node enlargement due to the present infection or at least one of the following symptoms of systemic infection: fever ≥ 38°C, lymphangitis, WBC (white blood cell) count ≥ 15,000 cells/μL, elevated C-reactive protein (> 5.0mg/L)
  • In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy

Exclusion Criteria:

  • A medical history of significant hypersensitivity or allergic reaction to quinolones, linezolid, vancomycin, or vancomycin derivatives
  • Women who are pregnant or lactating
  • Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response
  • Subjects with any of the following: infection involving prosthetic materials or foreign bodies, infection associated with a human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, toxic shock syndrome, gangrene, burns covering ≥ 10% of body surface area, severely impaired arterial blood supply, current evidence of deep vein thrombosis or superficial thrombophlebitis
  • Minor abscesses, unless present with one of the ABSSSI types
  • Any infection expected to require other antimicrobial agents in addition to study drug
  • Receipt of > 24 hours of systemic antibiotic therapy in the 14 days before enrollment unless one of the following is documented: the subject received a single dose of a short-acting antibacterial drug 3 or more days before clinical trial enrollment for surgical prophylaxis or recently completed treatment with an antibacterial drug for an infection other than ABSSSI and the drug does not have antibacterial activity against bacterial pathogens that cause ABSSSI
  • Receipt of more than 1 dose of a potentially effective antibacterial agent for treatment of the ABSSSI under study prior to enrollment
  • Receipt of chronic anti-inflammatory therapy for longer than 14 days before enrollment
  • Severely compromised immune systems
  • Subjects taking any medicinal product which inhibits monoamine oxidases A or B or within 2 weeks of Screening
  • Hypertension as defined by a systolic blood pressure of ≥ 180 mmHg or a diastolic blood pressure of ≥110 mmHg with confirmed re-check within 20 minutes of initial reading
  • Subjects with pheochromocytoma, thyrotoxicosis and/or subjects taking any of the following types of medications: sympathomimetic agents, vasopressive agents, dopaminergic agents, or other agents with the potential for serotonergic interactions
  • Subjects with carcinoid syndrome and/or subjects taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 (serotonin receptor) receptor agonists, meperidine, or buspirone
  • Known history of liver disease
  • History of severe renal impairment
  • Life expectancy of < 3 months
  • Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study
  • Subjects previously randomized in this study or in who have received a dose of an investigational drug within 30 days of randomization
  • Subjects > 140 kg in body weight

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Delafloxacin
300 mg IV (intravenous) every 12 hours for 5-14 days
300mg IV every 12 hours for 5-14 days
Other Names:
  • RX-3341
Active Comparator: Vancomycin
15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas
15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days
Other Names:
  • Vancocin
Active Comparator: Linezolid
600 mg IV every 12 hours for 5-14 days
600mg IV every 12 hours for 5-14 days
Other Names:
  • Zyvox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up
Time Frame: Follow-up (Day 14 ± 1)
The primary efficacy endpoint was the success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.
Follow-up (Day 14 ± 1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Erythema Clinical Success
Time Frame: 48 - 72 hours
The number of ITT subjects who had cessation of erythema within 48-72 hours, based on digital measurements, as well as resolution/absence of fever. Cessation was defined as a percentage change from baseline in total area of erythema/induration that is less than or equal to 0%.
48 - 72 hours
Pharmacokinetic (PK) Parameter, Area Under Curve, (AUCinf, ug*h/mL), in Subjects Administered Delafloxacin, Vancomycin, and Linezolid
Time Frame: Through Day 3 (± 1 day)
Blood samples for pharmacokinetic analyses were drawn from all subjects on Day 3 (± 1 day) of treatment within 2 hours before the first study drug infusion and at 1, 2, 3, 5, and 12 hours (ie, immediately before the second dose) after the start of the first study drug infusion. An analytical, validated method was used to analyze samples and determine human plasma concentrations. The primary pharmacokinetic parameter calculated was area under the plasma concentration - time curve from time 0 extrapolated to infinity (AUCinf, ug*h/mL).
Through Day 3 (± 1 day)
The Levels of Inflammation Were Examined by Measuring a Surrogate, C-Reactive Protein (CRP)
Time Frame: Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)
CRP Levels (g/m3) were analyzed from blood samples collected from subjects at Baseline and various time points throughout the study. Change in baseline values were analyzed using an analysis of covariance (ANCOVA) model with treatment, infection category, and prior antimicrobial therapy as fixed effects and the baseline measure as the covariate.
Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)
Microbiological Response Rate in All Subjects (Microbiological Evaluable Population)
Time Frame: Follow-up (Day 14 ± 1)
Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.
Follow-up (Day 14 ± 1)
Microbiological Response Rate in Subjects With MRSA (Methicillin Resistant Staphylococcus Aureus) in Microbiological Evaluable (ME) Population
Time Frame: Follow-up (Day 14 ± 1)
Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.
Follow-up (Day 14 ± 1)
Clinical Response in Subjects With Infections Caused by MRSA - Microbiological ITT (MITT) Population
Time Frame: Follow-up (Day 14 ± 1)
The success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.
Follow-up (Day 14 ± 1)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Scott Hopkins, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

January 24, 2011

First Submitted That Met QC Criteria

January 25, 2011

First Posted (Estimate)

January 26, 2011

Study Record Updates

Last Update Posted (Actual)

October 16, 2019

Last Update Submitted That Met QC Criteria

September 25, 2019

Last Verified

September 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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